Combined effects of cadmium and sulfamethoxazole on Eisenia fetida: Insights into accumulation, subcellular partitioning, biomarkers and toxicological responses.

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.

The discovery of a novel pyrrolo[2,3-b]pyridine as a selective CDK8 inhibitor offers a new approach against psoriasis.

Currently, the drugs used in clinical to treat psoriasis mainly broadly suppress cellular immunity. However, these drugs can only provide temporary and partial symptom relief, they do not cure the condition and may lead to recurrence or even serious toxic side effects. In this study, we describe the discovery of a novel potent CDK8 inhibitor as a treatment for psoriasis. Through structure-based design, compound 46 was identified as the most promising candidate, exhibiting a strong inhibitory effect on CDK8 (IC50 value of 57 nM) along with favourable inhibition against NF-κB. Additionally, it demonstrated a positive effect in an in vitro psoriasis model induced by TNF-α. Furthermore, this compound enhanced the thermal stability of CDK8 and exerted evident effects on the biological function of CDK8, and it had favourable selectivity across the CDK family and tyrosine kinase. This compound showed no obvious inhibitory effect on CYP450 enzyme. Further studies confirmed that compound 46 exhibited therapeutic effect on IMQ-induced psoriasis, alleviated the inflammatory response in mice, and enhanced the expression of Foxp3 and IL-10 in the dorsal skin in vivo. This discovery provides a new strategy for developing selective CDK8 inhibitors with anti-inflammatory activity for the treatment of psoriasis.

Clinical and Genetic Analysis of Multiple Idiopathic Cervical Root Resorption.

OBJECTIVE: To explore the genetic background and clinical phenotypes of multiple idiopathic cervical root resorption (MICRR) in a Chinese family. METHODS: The proband and his three family members were clinically examined and had radiographs taken with a radiovisiography (RVG) system and CBCT to define the diagnosis of MICRR. Genomic DNA (gDNA) was extracted from peripheral blood samples of the patient, his father, mother and younger sister for whole exome sequencing (WES). The pathogenicity of rare variants with minor allele frequency (MAF) less than 0.005 were analysed following possible inheritance patterns, predicted results from 12 software programs, the American College of Medical Genetics (ACMG) 2015 criteria, and information from ClinVar, OMIM and HGMD databases as well as gene function. RESULTS: The proband presented the typical MICRR phenotypes such as thin cervical pulp wall and apple core-like lesions in radiographs. Following the recessive inheritance pattern, WES analysis identified SHROOM2, SYTL5, MAGED1 and FLNA with a higher chance of causing MICRR. Four genes with compound heterozygous variants and another 27 genes with de novo variants either in autosomal-dominant or autosomal-recessive pattern were also found to have the potential pathogenicity. CONCLUSION: A total of 35 novel potential pathogenic genes were found to be associated with MICRR from a Chinese family through WES. The new genetic background of MICRR may be helpful for clinical and molecular diagnosis.

Quantification of Hop-Derived Bitter Compounds in Beer Using Liquid Chromatography Mass Spectrometry.

Hops (Humulus lupulus L.) are essential raw materials for beer brewing, and the major contributors to beer bitterness are isohumulones (iso-α-acids) and humulinones. In recent years, many breweries have focused on the production of hop-forward beer styles by adding hops after or during the cold fermentation stage, which will tend to release humulinones or other hop-derived bitter compounds. In this study, a LC-MS/MS method was developed for quantification of 60 hop-derived bitter compounds in 25 min. Reverse-phase chromatography with an alkaline methanol/acetonitrile (70:30) mobile phase was used for the separation. The quantitative range was 0.053-3912 ng/mL with correlation coefficient r > 0.99, and the LOQ were 0.26 and 0.053 ng/mL for iso-α-acids and humulinones. Precision (RSD < 5.0%) and accuracy (recovery 86.3%-118.1%) were both satisfactory. The abundance of hop-derived bitter compounds in the dry-hopped beer (Double-India Pale Ale) and the nondry-hopped beer (Vienna Lager) were monitored throughout the fermentation and storage stages, and the formation of oxidation and cyclization products showed difference profiles between these two beers. The quantification results reveal how hop-derived bitter compounds change throughout the brewing process, as well as the influence of hops and brewing techniques on beer bitterness.

TwinF interface inhibitor FP802 stops loss of motor neurons and mitigates disease progression in a mouse model of ALS.

Toxic signaling by extrasynaptic NMDA receptors (eNMDARs) is considered an important promoter of amyotrophic lateral sclerosis (ALS) disease progression. To exploit this therapeutically, we take advantage of TwinF interface (TI) inhibition, a pharmacological principle that, contrary to classical NMDAR pharmacology, allows selective elimination of eNMDAR-mediated toxicity via disruption of the NMDAR/TRPM4 death signaling complex while sparing the vital physiological functions of synaptic NMDARs. Post-disease onset treatment of the SOD1G93A ALS mouse model with FP802, a modified TI inhibitor with a safe pharmacology profile, stops the progressive loss of motor neurons in the spinal cord, resulting in a reduction in the serum biomarker neurofilament light chain, improved motor performance, and an extension of life expectancy. FP802 also effectively blocks NMDA-induced death of neurons in ALS patient-derived forebrain organoids. These results establish eNMDAR toxicity as a key player in ALS pathogenesis. TI inhibitors may provide an effective treatment option for ALS patients.

Physiological and behavioral basis of diamondback moth Plutella xylostella migration and its association with heat stress.

BACKGROUND: Migration is a strategy that shifts insects to more favorable habitats in response to deteriorating local environmental conditions. The ecological factors that govern insect migration are poorly understood for many species. Plutella xylostella causes great losses in Brassica vegetable and oilseed crops, and undergoes mass migration. However, the physiological and behavioral basis for distinguishing migratory individuals and the factors driving its migration remain unclear. RESULTS: Daily light trap catches conducted from April to July in a field population of P. xylostella in central China revealed a sharp decline in abundance from late-May. Analysis of ovarian development levels showed that the proportion of sexually immature females gradually increased, while the mating rate decreased, indicating that generations occurring in May mainly resulted from local breeding and that emigration began in late-May. Physiological and behavioral analyses revealed that emigrant populations had a higher take-off proportion, stronger flight capacity and greater energy reserves of triglyceride compared to residents. Furthermore, a gradual increase in temperature from 24 °C to >30 °C during larval development resulted in a significant delay in oogenesis and increased take-off propensity of adults compared with the control treatment reared at a constant temperature of 24 °C. CONCLUSION: Our results provide the physiological and behavioral factors that underpin mass migration in P. xylostella, and demonstrate that exposure to increased temperature increases their migration propensity at the cost of reproductive output. This study sheds light on understanding the factors that influence population dynamics, migratory propensity and reproductive tradeoffs in migratory insects. © 2023 Society of Chemical Industry.

Sanguinarine modulates microglial function via PPARγ activation and protects against CNS demyelination.

Microglia aggregate in regions of active inflammation and demyelination in the CNS of multiple sclerosis (MS) patients and are considered pivotal in the disease process. Targeting microglia is a promising therapeutic approach for myelin repair. Previously, we identified two candidates for microglial modulation and remyelination using a Connectivity Map (CMAP)-based screening strategy. Interestingly, with results that overlapped, sanguinarine (SAN) emerged as a potential drug candidate to modulate microglial polarization and promote remyelination. In the current study, we demonstrate the efficacy of SAN in mitigating the MS-like experimental autoimmune encephalomyelitis (EAE) in a dose-dependent manner. Meanwhile, prophylactic administration of a medium dose (2.5 mg/kg) significantly reduces disease incidence and ameliorates clinical signs in EAE mice. At the cellular level, SAN reduces the accumulation of microglia in the spinal cord. Morphological analyses and immunophenotyping reveal a less activated state of microglia following SAN administration, supported by decreased inflammatory cytokine production in the spinal cord. Mechanistically, SAN skews primary microglia towards an immunoregulatory state and mitigates proinflammatory response through PPARγ activation. This creates a favorable milieu for the differentiation of oligodendrocyte progenitor cells (OPCs) when OPCs are incubated with conditioned medium from SAN-treated microglia. We further extend our investigation into the cuprizone-induced demyelinating model, confirming that SAN treatment upregulates oligodendrocyte lineage genes and increases myelin content, further suggesting its pro-myelination effect. In conclusion, our data propose SAN as a promising candidate adding to the preclinical therapeutic arsenal for regulating microglial function and promoting myelin repair in CNS demyelinating diseases such as MS.

Combined inhibitory effects of microcystin-LR and microcystin-RR on growth and development in zebrafish larvae.

Microcystins (MCs) are the most widespread, frequently found, and seriously toxic cyanobacterial toxins in aquatic environments. Microcystin-leucine-arginine (MCLR) and microcystin-arginine-arginine (MCRR) are the most studied MCs. Normally, their levels are low and they coexist in the environment; however, they may also interact with each other. The developmental toxicity of MCLR in the presence of MCRR in the early life stage of zebrafish (from 2 to 120 h post fertilization) was investigated for the first time in this study. Our findings revealed that MCRR treatment marginally elevated thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels, whereas MCLR treatment alone resulted in a significant increase in T3 and T4 levels, indicating a cooperative effect. Furthermore, clear changes in the expression levels of genes involved in growth and development, accompanied by growth inhibition, were observed after co-treatment with MCRR and MCLR. In addition, zebrafish larvae subjected to MCRR and/or MCLR treatment showed increased levels of superoxide dismutase, glutathione, and malondialdehyde, and decreased levels of catalase in the MCRR + MCLR group, indicating oxidative stress and lipid peroxidation. Thus, we investigated the synergistic developmental toxicity of MCRR and MCLR during the early life stages of zebrafish development.

Enhancement of tolerance against flonicamid in Solenopsis invicta (Hymenoptera: Formicidae) through overexpression of CYP6A14.

Solenopsis invicta is a main issue in southern China and is causing significant damage to the local ecological environment. The extensive use of insecticides has resulted in the development of tolerance in S. invicta. In our study, ten S. invicta colonies from Sichuan Province exhibited varying degrees of tolerance against flonicamid, with LC50 values from 0.49 mg/L to 8.54 mg/L. The sensitivity of S. invicta to flonicamid significantly increased after treatment with the P450 enzyme inhibitor piperonyl butoxide (PBO). Additionally, the activity of P450 in S. invicta was significantly enhanced after being treated with flonicamid. Flonicamid induced the expression levels of CYP4aa1, CYP9e2, CYP4C1, and CYP6A14. The expression levels of these P450 genes were significantly higher in the tolerant colonies compared to the sensitive colonies, and the relative copy numbers of CYP6A14 in the tolerant colonies were 2.01-2.15 fold. RNAi feeding treatment effectively inhibited the expression of P450 genes, thereby reducing the tolerance of S. invicta against flonicamid. In addition, the overexpression of CYP6A14 in D. melanogaster resulted in reduced sensitivity to flonicamid. Our investigations revealed hydrophobic interactions between flonicamid and seven amino acid residues of CYP6A14, along with the formation of a hydrogen bond between Glu306 and flonicamid. Our findings suggest that flonicamid can effectively control S. invicta and P450 plays a pivotal role in the tolerance of S. invicta against flonicamid. The overexpression of CYP6A14 also increased tolerance to flonicamid.

Interocular Symmetry in Retinal Nerve Fiber Layer Thickness in Children: The Hong Kong Children Eye Study.

INTRODUCTION: The aim of this work is to determine the interocular differences in peripapillary retinal nerve fiber layer (p-RNFL) thickness and its associations among school children in Hong Kong. METHODS: We conducted a population-based study including 4034 children aged 6-8 years from the Hong Kong Children Eye Study (HKCES). All participants received comprehensive ocular examinations where p-RNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). The degree of symmetry between both eyes was analyzed and represented by intraclass correlation coefficient (ICC) values. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with p-RNFL thickness difference. RESULTS: The study included 4034 children with a mean age of 7.61 ± 0.98 years. The mean global p-RNFL thickness was 106.60 ± 9.41 µm in right eyes and 105.99 ± 9.30 µm in left eyes. The ICC for global p-RNFL difference was 0.866 (95% CI 0.858-0.873, p < 0.001). The symmetry displayed the largest values in nasal inferior quadrant with the ICC value of 0.736 (95% CI 0.721-0.749); and the smallest degree of symmetry was found to be in the superior temporal quadrant with the ICC value of 0.567 (95% CI 0.546-0.588). Axial length (AL) difference was found to have more pronounced correlation to interocular symmetry in p-RNFL thickness with the coefficient of 0.514 (p < 0.001). CONCLUSIONS: Normal variation in interocular symmetry exists in children. Our results can contribute to the establishment of a standard reference for interocular differences in OCT parameters in children. The interocular differences in AL should be considered in the interpretation of RNFL symmetry, in terms of identifying children at risk of developing glaucoma or other ocular disorders.

Secondhand smoke exposure and ocular health: A systematic review.

The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms-supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health.

IL-10-dependent Effect of Chinese Medicine Abelmoschus manihot on Alleviating Intestinal Inflammation and Modulating Gut Microbiota.

Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10[Formula: see text]). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF-[Formula: see text] levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10[Formula: see text] mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae, Sutterellaceae, Erysipelotrichaceae, Burkholderiaceae, Desulfovibrionaceae, and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.

Analysis of Secondhand Smoke Exposure and Myopia Among Children Aged 6 to 8 Years in Hong Kong.

Importance: Secondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown. Objective: To examine the association between SHS exposure and childhood myopia. Design, Setting, and Participants: Cross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations. Exposure: Secondhand smoke exposure. Main Outcomes and Measures: Generalized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset. Results: A total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (ß = -0.09 [95% CI, -0.14 to -0.03]) and longer axial length (ß = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child's exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (ß = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (ß = -0.05 [95% CI, -0.08 to -0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (ß = -0.07 [95% CI, -0.11 to -0.02]), axial length (ß = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (ß = -1.30 [95% CI, -2.32 to -0.27]). Conclusions and Relevance: The findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.

Crosslinking for post-laser-assisted in situ keratomileusis corneal ectasia: Transepithelial flap-on 30 minute and flap-lift 4 minute protocol.

Purpose: To evaluate the outcomes of transepithelial corneal collagen crosslinking (CXL) for management of corneal ectasia after laser-assisted in situ keratomileusis (LASIK). Methods: CXL was performed on 18 eyes of 16 patients either with LASIK flap lift (n = 9; 365 nm, 30 mW/cm2, 4 minutes, pulse) or with transepithelial flap-on (n = 9 eyes; 365 nm, 3 mW/cm2, 30 minutes) technique. Postoperative change in maximum keratometry (Kmax), anterior elevation, posterior elevation, spherical equivalent (SE), logMAR uncorrected distance visual acuity (UDVA), aberrations, and central corneal thickness (CCT) were evaluated at 12 months postoperatively. Results: A total of 18 eyes of 16 patients (11 males, 5 females) were included. Overall, Kmax flattened more after flap-on CXL (P = 0.014) compared to flap-lift CXL. The endothelial cell density and posterior elevation were stable throughout the follow-up period. Index of vertical asymmetry (IVA), keratoconus index (KI), and central keratoconus index (CKI) decreased after flap-on CXL at 12 months, postoperatively (P < 0.05), whereas there were no statistically significant changes in these parameters after flap-off CXL group. The spherical aberrations and total root mean square decreased after flap-lift CXL at 12 months, postoperatively (P < 0.05). Conclusion: In our study, transepithelial collagen crosslinking was successfully used to halt disease progression in post-LASIK keratectasia. We recommend flap-on surgical technique for these cases.

Prevalence and Characteristics of Peripapillary Gamma Zone in Children With Different Refractive Status: The Hong Kong Children Eye Study.

Purpose: This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children. Methods: Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans. The Bruch's membrane opening (BMO) was identified in over 48 meridians in each eye. The peripapillary gamma zone was defined as the region between the BMO and the border of the optic disc, identified by the OCT. Results: The prevalence of the peripapillary gamma zone was higher in myopic eyes (36.3%) than in emmetropic (16.1%) and hyperopic eyes (11.5%, P < 0.001). AL (per 1 mm; odds ratio [OR]) = 1.861, P < 0.001) and a more oval disc shape (OR = 3.144, P < 0.001) were associated with the presence of a peripapillary gamma zone after adjusting for demographic, systemic, and ocular variables. In the subgroup analysis, a longer AL was associated with the presence of a peripapillary gamma zone in myopic eyes (OR = 1.874, P < 0.001), but not in emmetropic (OR = 1.033, P = 0.913) or hyperopic eyes (OR = 1.044, P = 0.883). A peripapillary zone was not observed in the region nasal to the optic nerve in myopic eyes, in contrast to its presence in the same region in 1.9% of emmetropic eyes and 9.3% of hyperopic eyes; these intergroup differences were statistically significant (P < 0.001). Conclusions: Although peripapillary gamma zones were observed in the eyes of both myopic and non-myopic children, their characteristics and distribution patterns were substantially different.

Discovery of a novel oral type â CDK8 inhibitor against acute myeloid leukemia.

CDK8 plays a key role in acute myeloid leukemia, colorectal cancer and other cancers. Here, a total of 54 compounds were designed and synthesized. Among them, the most potent one compound 43 (3-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide), a novel CDK8 Ⅰ inhibitor, showed strong inhibitory activity against CDK8 (IC50 = 51.9 nM), good kinase selectivity, good anti AML cell proliferation activity (molm-13 GC50 = 1.57 ± 0.59 µM) and low toxicity in vivo (acute toxicity: 2000 mg/kg). Further mechanistic studies revealed that this compound could target CDK8 and then phosphorylate STAT-1 and STAT-5 thereby inhibiting of AML cell proliferation. In addition, compound 43 showed relatively good bioavailability (F = 28.00%) and could inhibit the growth of AML tumors in a dose-dependent manner in vivo. This study facilitates the further development of more potent CDK8 inhibitors for the treatment of the AML.

Chemical constituents and biological activities of Artemisia argyi H.Lév. & vaniot.

Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide and ODS CC and HPLC. The structures of all compounds are determined by 1 D NMR (1H-NMR、13C-NMR) and literature comparison. Among them, compounds 1 and 8 were isolated from Chinese folk medicine A. argyi for the first time. Besides, the LPS-induced RAW264.7 cell model has been evaluated the anti-inflammatory activities in vitro by the Griess reagent. The results indicated that the guaianolide sesquiterpenoids obtained from A. argyi have an excellent ability to inhibit NO production, especially Argyin A, a guaianolide sesquiterpenoid with isovaleryloxy substitution.

Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children.

PURPOSE: Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications. METHODS: 2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression. RESULTS: SNPs rs33912345 (p=7.7×10-4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8-9 year-old group for rs33912345 (p=5.2×10-4) and rs10483727 (p=3.3×10-4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (ß=1.66; p=0.0059), but not rs33912345-C (ß=1.31; p=0.052) or rs10483727-T (ß=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL. CONCLUSIONS: Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.

Differential compensatory role of internal astigmatism in school children and adults: The Hong Kong Children Eye Study.

BACKGROUND: To compare the prevalence of refractive (RA), corneal (CA), and internal astigmatism (IA) in Hong Kong children and adults and evaluate the role of IA in compensating for total astigmatism and its relations to myopic traits. METHODS: The Hong Kong Children Eye Study is a population-based cross-sectional study. Totally 3704 school children (mean age 7.5 ± 1.0 years) and 5577 adults (mean age 41.1 ± 7.5 years), who were their parents, were recruited. Cycloplegic and non-cycloplegic refractive cylinders were obtained from children and adults, respectively. Spearman correlation was applied to detect associations between astigmatism, ocular biometrics, refraction, and lens power. Astigmatism compensation factor (CF) was derived from the power vector analysis J0 and J45. RESULTS: The prevalence of RA (≤-1.0 D), CA (≥+1.0 D) and IA (≥+1.0 D) was 21.9%, 63.9%, and 9.9% in children, and 30.9%, 39.5%, and 23.7% in adults respectively. The mean RA, CA and IA values in children and adults were -0.69 ± 0.66 D, +1.14 ± 0.61 D, +0.62 ± 0.32 D, and -0.80 ± 0.74 D, +0.97 ± 0.69 D, and +0.76 ± 0.43 D, respectively. In adults and children, IA was negatively correlated with axial length (p < 0.0001), but positively correlated with spherical values and equivalent (p < 0.0001), suggesting an association of astigmatism with myopic traits. A greater proportion of children exhibited compensation by IA than adults in J0 (86.6% vs. 66.0%, p < 0.0001) and J45 components (55.5% vs. 41.7%, p < 0.0001). CONCLUSIONS: Chinese children in Hong Kong exhibit a higher prevalence of RA and CA than in other cities. Children displayed a greater compensation by IA than adults, suggesting an age-related attenuation of IA compensation. IA is associated with myopic traits.